TY - JOUR
T1 - Effect of 5-Azacitidine Treatment on Redox Status and Inflammatory Condition in MDS Patients
AU - Montes, Paola
AU - Guerra-Librero, Ana
AU - García, Paloma
AU - Cornejo-Calvo, María Elena
AU - López, María Del Señor
AU - de Haro, Tomás
AU - Martínez-Ruiz, Laura
AU - Escames, Germaine
AU - Acuña-Castroviejo, Darío
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1
Y1 - 2022/1
N2 - This study focused on the impact of the treatment with the hypomethylating agent 5-azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded, and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD; catalase, CAT; glutathion peroxidase, GPx; and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, as well as CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, as well as increased CAT activity compared with healthy subjects, with no changes in SOD, GPx, and GRd activities, or AOPP levels. When analyzing the evolution from early to advanced stages of the disease, we found that the GPx activity, GSSG/GSH ratio, LPO, and AOPP increased, with a reduction in CAT. GPx changes were related to the presence of risk factors such as high-risk IPSS-R or mutational score. Moreover, there was an increase in IL-2, IL-6, IL-8, and TNF-α plasma levels, with a further increase of IL-2 and IL-10 from early to advanced stages of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generated oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.
AB - This study focused on the impact of the treatment with the hypomethylating agent 5-azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded, and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD; catalase, CAT; glutathion peroxidase, GPx; and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, as well as CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, as well as increased CAT activity compared with healthy subjects, with no changes in SOD, GPx, and GRd activities, or AOPP levels. When analyzing the evolution from early to advanced stages of the disease, we found that the GPx activity, GSSG/GSH ratio, LPO, and AOPP increased, with a reduction in CAT. GPx changes were related to the presence of risk factors such as high-risk IPSS-R or mutational score. Moreover, there was an increase in IL-2, IL-6, IL-8, and TNF-α plasma levels, with a further increase of IL-2 and IL-10 from early to advanced stages of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generated oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.
KW - 5-azacitidine
KW - Cytokines
KW - Inflammation
KW - Myelodysplastic syndrome (MDS)
KW - Oxidative stress
KW - Somatic alterations
UR - http://www.scopus.com/inward/record.url?scp=85122352006&partnerID=8YFLogxK
U2 - 10.3390/antiox11010139
DO - 10.3390/antiox11010139
M3 - Article
AN - SCOPUS:85122352006
SN - 2076-3921
VL - 11
JO - Antioxidants
JF - Antioxidants
IS - 1
M1 - 139
ER -